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Keywords:

  • BMP4;
  • anterior heart field;
  • mouse;
  • Cre;
  • Mef2c;
  • semilunar valve;
  • endocardial cushion;
  • outflow tract;
  • ventricular septal defect

Abstract

The endocardial cushions play a critical role in septation of the four-chambered mammalian heart and in the formation of the valve leaflets that control blood flow through the heart. Within the outflow tract (OFT), both cardiac neural crest and endocardial-derived mesenchymal cells contribute to the endocardial cushions. Bone morphogenetic protein 4 (BMP4) is required for endocardial cushion development and for normal septation of the OFT. In the present study, we show that anterior heart field (AHF)–derived myocardium is an essential source of BMP4 required for normal endocardial cushion expansion and remodeling. Loss of BMP4 from the AHF in mice results in an insufficient number of cells in the developing OFT endocardial cushions, defective cushion remodeling, ventricular septal defects, persistent truncus arteriosus, and abnormal semilunar valve formation. Developmental Dynamics 237:3200–3209, 2008. © 2008 Wiley-Liss, Inc.